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Biomedical subjects

N Takeda

Publications and source records attributed to N Takeda.

At least 19 recordsLinked to original sources
PubMed1995

Mesodermal defect in late phase of gastrulation by a targeted mutation of focal adhesion kinase, FAK.

FAK is a unique non-receptor protein tyrosine kinase that was found in cellular focal adhesions. An increasing number of in vitro observations has suggested that FAK mediates signaling through integrins brought about by interactions with extracellular matrix (ECM). It is highly tyrosine-phosphorylated in v-src-transformed cells and during embryogenesis. To clarify the function of FAK in cell-ECM interactions, embryonic phenotype of its mutant was analysed. FAK-deficient embryos could implant and initiate gastrulation normally, but showed abnormalities in subsequent development. The abnormalities were characterized as a general deficiency in mesoderm, and the phenotype was quite similar to that caused by fibronectin-deficiency. The results suggest that FAK mediates fibronectin-integrin interactions uniquely at this stage of development, thereby playing an essential role in development of mesodermal cell lineages.

Animals↗
PubMed1995

Mouse Otx2 functions in the formation and patterning of rostral head.

The anterior part of the vertebrate head expresses a group of homeo box genes in segmentally restricted patterns during embryogenesis. Among these, Otx2 expression covers the entire fore- and midbrains and takes place earliest. To examine its role in development of the rostral head, a mutation was introduced into this locus. The homozygous mutants did not develop structures anterior to rhombomere 3, indicating an essential role of Otx2 in the formation of the rostral head. In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is not expressed. The homo- and heterozygous mutant phenotypes suggest Otx2 functions as a gap-like gene in the rostral head where Hox code is not present. The evolutionary significance of Otx2 mutant phenotypes was discussed for the innovation of the neurocranium and the jaw.

Abnormalities, Multiple↗
PubMed1995

Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice.

The intracellular protein tyrosine kinase FAK (focal adhesion kinase) was originally identified gy its high level of tyrosine phosphorylation in v-src-transformed cells. FAK is also highly phosphorylated during early development. In cultured cells it is localized to focal adhesion contacts and becomes phosphorylated and activated in response to integrin-mediated binding of cells to the extracellular matrix, suggesting an important role in cell adhesion and/or migration. We have generated FAK-deficient mice by gene targeting to examine the role of FAK during development. Mutant embryos displayed a general defect of mesoderm development, and cells from these embryos had reduced mobility in vitro. Surprisingly, the number of focal adhesions was increased in FAK-deficient cells, suggesting that FAK may be involved in the turnover of focal adhesion contacts during cell migration.

Animals↗
PubMed1995

Pressure- and thermally-induced reversible changes in the secondary structure of ribonuclease A studied by FT-IR spectroscopy.

Fourier transform infrared (FT-IR) spectroscopy combined with a resolution enhancement technique has been used to characterize pressure and thermal effects on the secondary structure of ribonuclease A. The experiments were performed at pD 7.0 with 50 mg/mL protein solution in D2O buffer. According to the observed changes in the amide I' band, secondary structure elements such as alpha-helices, beta-sheets, and turns are cooperatively disrupted by application of either pressures above 570 MPa at 30 degrees C or temperatures above 60 degrees C at 0.1 MPa. Pressure- and thermally-denatured ribonuclease A are fully unfolded and do not contain any residual secondary structures. Both the structural changes are intrinsically reversible, although the pressure-induced transition shows a hysteresis. It is found that nonnative turn structures are formed prior to the appearance of the native secondary structure in the folding from the pressure-unfolded state. The structural features upon the pressure-induced unfolding are additionally characterized by the interesting behavior of hydrogen-deuterium exchange at high pressure. Most of the backbone amide protons protected at atmospheric pressure, which are involved in the alpha-helices and beta-sheet, are exchanged with solvent deuterons in the pressure range where the two secondary structural elements are virtually identified as intact. There is a possibility that, for ribonuclease A, application of high pressure up to 570 MPa induces such a partially unfolded state as has native-like secondary structure but permits solvent to be highly accessible to the internal regions.

Animals↗
PubMed1995

Femoral peak bone mass and osteoclast number in an animal model of age-related spontaneous osteopenia.

BACKGROUND: SAMP6 was developed as a murine model of age-related spontaneous osteopenia characterized by low peak bone mass. A morphometric study of the growing femur in SAMP6 and sex-matched SAMP2 at 10 days to 4 months of age was done to examine the pathogenic process related to osteopenia. METHODS: Age-related changes in cortical bone thickness, femur score, trabecular bone volume, thickness of epiphyseal growth plate, number of osteoclasts, and osteoclast surface were measured with a computerized image analyzer. Osteoclasts were examined cytomorphometrically after TRAP (tartrate resistant acid phosphatase) staining of the femoral sections. RESULTS: Cortical bone thickness and femur score increased significantly with age, while trabecular bone volume decreased significantly. Comparing mean values of cortical bone thickness, femur score and trabecular bone volume, we noted significantly lower mean values in SAMP6 than in SAMP2 mice. These significant inter-stain differences first became evident in 20-40-day-old mice, but there was no significant difference in thickness of the epiphyseal growth plate between the two strains. The mean values of the number of osteoclasts per unit bone surface length and of the osteoclast surface in SAMP6 were significantly greater than in age- and sex-matched SAMP2. Histograms of distribution of size of osteoclasts of 40-day-old male mice revealed that larger ones were more frequently seen in SAMP6. Furthermore, the ratio of osteoclasts/TRAP positive cells free in the bone marrow cavity was significantly higher in SAMP6 than in SAMP2. CONCLUSION: Activated bone resorption may play a role in the osteopenia seen in SAMP6.

Aging↗
PubMed1995

Vascularized fibular graft for bone reconstruction of the extremities after tumor resection in limb-saving procedures.

We treated 18 patients (8 males and 10 females) with bone or soft tissue tumors in the extremities by vascularized fibular grafts (VFGs). The average age was 29 years. Two had malignant soft tissue tumors in the forearm (angiosarcoma and synovial sarcoma) and the other 16 had bone tumors [osteosarcoma (8), chondrosarcoma (3), angiosarcoma (1), adamantinoma (1), and giant cell tumor (3)]. Affected sites of the bone tumor cases were tibia (5), femur (5), humerus (3), radius (2), and ulna (1). According to the surgical staging system of Enneking et al. 1 patient was in stage III, 12 in IIB, 2 in IB, and 3 in IA. The surgical margin was curative in 5 patients, wide in 9, marginal in 2, and intralesional in 2. One patient died due to lung metastasis although bone union was obtained by the VFGs. Functional results of the bone reconstruction in the remaining 17 patients were evaluated according to the modified scale of Enneking et al. The VFGs resulted in substantial bone unions in all patients except 1. Bone unions in all 17 patients occurred in less than 10 months. Overall clinical results were satisfactory. Based on a 30-point scale overall clinical results ranged from 10 to 30 points with an average of 21 points. Functional evaluation in the upper extremity were, generally, superior to those in the lower extremity. Postoperative complications were 5 metastases (4 in the lung and 1 in the mediastinum) in 4 patients, 1 recurrence, and 2 fractures after obtaining bone union. One patient died from metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

A new strategy of gene trapping in ES cells using 3'RACE.

"Gene trapping" in embryonic stem (ES) cells is a novel approach to identify a series of genes in mammals concomitant with the production of the corresponding mutant mice. However, this approach is currently unable to identify genes that are not expressed in ES cells. Here we describe a strategy to identify gene trapping clones which is not based on expression of a reporter gene. It uses the neor gene which lacks a polyadenylation signal and has a splice donor signal. Expression of the neor gene as fusion transcripts with the 3' end containing the polyadenylation signal of tagged genes allows the identification of these clones by 3' rapid amplification of the cDNA end in undifferentiated ES cells, even if the genes are not expressed in ES cells. Amplification was observed in about 25% of G418-resistant clones. Sequence analyses suggested the amplifications represent gene trapping events. The feasibility of this approach was further assessed by analysing one clone, PAT-12, in detail.

Amino Acid Sequence↗
PubMed1995

Favorable course of steroid-responsive nephrotic children with mild initial attack.

The course and prognosis of idiopathic nephrotic syndrome has thus far not been found to be predicted from the severity of the manifestations at the onset. Among 66 steroid-responsive nephrotic children, eight were asymptomatic without edema and identified by chance proteinuria on a urinary screening program. The selectivity index for proteinuria (a clearance ratio of IgG to transferrin) was 0.10 or less in all of the five children examined. All of the eight children responded quickly to the prednisolone therapy. Grades of proteinuria and hypoalbuminemia were lower in the asymptomatic children than in the symptomatic children who presented with edema. Median proteinuria levels were 2.0 versus 4.2 g/day/m2 (P < 0.01), respectively, and mean serum albumin levels were 2.2 +/- 0.3 versus 1.8 +/- 0.4 g/dl (mean +/- SD; P < 0.01), respectively. None of the eight asymptomatic children relapsed for at least one year after completion of the prednisolone treatment, while, in contrast, 30 of 58 symptomatic nephrotic children relapsed during the same one-year period (P < 0.01). These findings suggest that, among steroid-responsive nephrotic children, those with mild manifestations without edema may have a milder disease and show an extremely favorable clinical course.

Child↗
PubMed1995

Ovarian teratomas in mice lacking the protooncogene c-mos.

Parthenogenesis has been suggested to be tightly coupled with development of ovarian teratomas. Indeed, ovarian tumors developed in c-mos-deficient female mice, which are characterized by the parthenogenetic activation of oocytes. The tumors appeared at a frequency of 30% between 4 and 8 months of age, and did not develop in younger or older mice. Most of the tumors were benign and consisted of multi-focal cysts most notably with mature ectodermal components, but also with mesodermal and endodermal components. One among 17 tumors observed consisted of extra-embryonic tissues alone, and two bore malignant components with metastasis to peritoneal organs. The results strongly suggest the involvement of c-mos mutations in human germ cell tumors.

Age Factors↗
PubMed1995

[A clinical study of six cases of toxic shock-like syndrome by group A Streptococcus].

We have encountered six cases with toxic shock-like syndrome (TSLS) by Group A Streptococcus since 1978. Every patient had from the onset flu-like symptoms or high fever and immediately developed some of the following clinical signs: hypotension, acute renal failure, disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS). Three of the six patients died with rapid clinical courses and three survived. As for the surviving patients, early administration of antibiotics and anti-DIC therapy were effective. Streptococcus pyogenes were isolated from the blood in five of the patients, ascites from another, and necrotizing tissue in one patient. The serovars of the isolated strains were typed as T1/M1 in three, T8 in one, and T28 in another. The toxin-type of the strains were typed as B in four and B + C in one. Though there have been few reports of TSLS before 1992 in Japan, it is supposed that many TSLS cases may have potentially occurred.

Aged↗
PubMed1995

Elevated serum levels of 3-deoxyglucosone, a potent protein-cross-linking intermediate of the Maillard reaction, in uremic patients.

3-Deoxyglucosone (3-DG) has been identified as an intermediate of the Maillard reaction in vitro. We measured serum 3-DG levels using gas chromatography/mass spectrometry and found a marked elevation in serum 3-DG levels in uremic patients compared with healthy subjects. The uremic patients with diabetes showed significantly higher serum concentrations of 3-DG than those without diabetes. 3-DG was demonstrated to be a potent protein-cross-linking agent in the reaction with lysozyme, leading to browning, fluorescence formation and polymerization of the protein by formation of advanced glycation end products (AGE). The increase in serum 3-DG levels in the uremic patients suggests that 3-DG may be responsible for the development of uremic complications by promoting the formation of AGE.

Adult↗
PubMed1995

A study on urine cotinine for the evaluation of smoking cessation.

Two branch offices of enterprise T in the same city engaged in service and sales were selected at random for this study on the evaluation of smoking cessation education using the urine cotinine concentration (U-Cot) measured by ion pair reversed-phase high performance liquid chromatography (IP-R-HPLC). Branch A conducted a smoking cessation education program; branch B did not. By comparison of the results obtained from questionnaires and U-Cot analyses at both the offices, we investigated the validity of evaluation by U-Cot. The results were as follows: I. Smokers 1. At branch A, a self-reported 20-year-old female non-smoker was confirmed to smoke about 5 cigarettes per day by her high concentration (292.8) of U-Cot at pre-education. 2. At branch A, the self-reported average number of cigarettes smoked daily (ANCSD) at 6 months post-education showed a significant decrease in comparison with that at pre-education. 3. At branch A, U-Cot at post-education showed a significant decrease in comparison with those at 2 weeks, 2 months, and 6 months pre-education in descending order. 4. Two male subjects who were strongly suspected to have submitted a false number of cigarettes smoked prior to urine sampling (NCSPU)/ANCSD self-reports at 6 months post-education were confirmed to have done so by the U-Cot values at the fourth period, which were in excess of 500, and the discrepancy between the ratio ([value at post-education in 6 months] divided by [value at pre-education]) of U-Cot (1.52, 1.47, respectively) and that of NCSPU/ANCSD, (0.00)/0.00). 5. At branch A, discrepancies between the success rate of quitting smoking in self-reported NCSPU/ANCSD at 6 months (17.0%) and in U-Cot (12.2%) were observed. At branch B, no such discrepancies were observed. 6. At branch A, office workers at 6 months post-education who had, but not those who had not, previously considered the health damage caused by smoking showed a significant decrease in NCSPU/ANCSD, and also in U-Cot at 2 weeks, 2 months and 6 months post-education. At branch B, no such differences were observed. 7. At branch A, office workers at 6 months post-education who had previously considered quitting smoking showed a significant decrease in NCSPU/ANCSD, and also in U-Cot at 2 weeks, 2 months and 6 months post-education. Those who had not previously considered quitting showed a significant decrease in ANCSD, but not in NCSPU or U-Cot.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Assessment of auditory and vestibular functions after vestibular neurectomy for Menière's disease.

Fourteen patients (12 Meniere's disease, one delayed endolymphatic hydrops and one labyrinthitis) suffering from intractable vertigo were treated with retrosigmoid vestibular neurectomy (RSVN) in our institute. Dizziness was controlled completely in all patients. Hearing was preserved in 91.7% of the cases with pure tone threshold deteriorating by more than 10 dB in one case, remained unchanged in 10 cases and improved in one case during long term observation. Substantial decrease of tinnitus was observed in 78.6%. Vestibular compensation was chronologically analyzed with a stabilometer, ENG and vestibular rotation test (0.01-0.64 Hz). Vestibular compensation under static conditions was accomplished within 2 weeks, except for spontaneous nystagmus measured in the dark. Asymmetry of vestibulo-ocular reflex was noted 2 weeks after the operation but had disappeared after 4 weeks. However, for over 2 years the VOR time constant remained lower (4.3-5.2 s) than the pre-operative value (8.2 s). Electro-cochleogram (ECoG) was recorded before and after RSVN. The -SP/AP ratio tended to increase after RSVN in the operated ear, though there was no change in the contralateral ear. The efferent olivo-cochlear bundle was thought to play a potential role in this increase of the -SP/AP ratio.

Adult↗
PubMed1995

Natural history of intracranial cavernous malformations.

The authors have reviewed the clinical records of 110 patients with intracranial cavernous malformations diagnosed by histological examination and/or magnetic resonance imaging over a mean follow-up period of 4.71 years. These cases were divided, based on their presentation, into a hemorrhage group, a seizure group, and an incidentally diagnosed group. The rate of subsequent symptomatic bleeding was investigated in relation to age at onset, sex, and location of the initial lesion. A high rate of subsequent symptomatic bleeding episodes was found in the hemorrhage group, especially among younger females. The nonhemorrhagic-onset cases had a very low incidence of bleeding. The outcome was generally good, except in patients with lesions in the basal ganglia and brainstem. These findings will be helpful in planning a rational therapeutic strategy for intracranial cavernous malformations.

Adolescent↗